A New Synthesis of Poly Heterocyclic Compounds Containing [1,2,4]triazolo and [1,2,3,4]tetrazolo Moieties and their DFT Study as Expected Anti-cancer Reagents

Abstract

Background: 2-amino-3-cyanopyridines are good starting reagents that have been used in synthesis of many heterocyclic compounds such as pyridopyrimidines, [1,2,4]triazolo and [1,2,3,4] tetrazolo derivatives which have biological activities as anti-microbial and cytotoxic activities. Meanwhile [1,2,4]triazolo and [1,2,3,4]tetrazolo derivatives are well known to possess many physiological activities, such as anticancer , antifungal, muscle relaxant, hypnotic, anti-inflammatory, diuretic and antihypertensive activities. A broad class of heterocyclic compounds has been studied to demonstrate their biological activity on the structures of DNA and RNA. Several of important functions make Tankyrases acts as targets in potential drug. Objective: The article focuses on synthesis of [1,2,4]triazolo and [1,2,3,4]tetrazolo derivatives and their theoretical calculations that suggest they are anti-cancer substances. Materials and Methods: DFT and computational studies were performed on the structural properties of experimental molecules experimentally, and significant theoretical calculations were performed based on density functional theory (DFT) with Becke’s three-parameter exchange function21-22 of correlation functional Lee Yang Parr (B3LYP) with the basis set 6-31G (d,p) using Gaussian 03 software23. Geometrical parameters of the optimized structures were calculated and also the charge on each atom (Mulliken charge). Chemcraft program24 was used to visualize the optimized structure and ChemBio3D ultra 12.0 was used to visualize the highest occupied and lowest unoccupied molecular orbitals. Results: Preliminary screening in five studied ligands acts as inhibitors for different active sites along the target. The molecular docking study also revealed that the compound 6c was the most effective compounds in inhibiting Tankyrase I enzyme (2rf5), this result can help strongly in inhibition of carcinogenic cells and cancer treatment. Conclusion: We have described a new practical cyclocondensation synthesis for a series of [1,2,4]triazolo[4,3- c]pyrido[3,2-e] pyrimidine and pyrido[2',3':4,5] pyrimido[6,1-c][1,2,4] triazine from 2-amino-3-cyano-4.6- diarylpyridines. Also polyheterocyclic compounds containing [1,2,4]triazolo and [1,2,3,4]tetrazolo moieties were also synthesized through the reactions of 3-hydrazino-8,10-diaryl [1,2,4]triazolo[4,3-c]pyrido[3,2- e]pyrimidine with both formic acid and the formation of diazonuim salt respectively. Newly synthesized heterocycles structures were confirmed using elemental analysis, IR, 1H-NMR, 13C-NMR and mass spectral data. DFT and computational studies were carried out on five of the synthesized poly heterocyclic compounds to show their structural and geometrical parameters involved in the study. Molecular docking using Tankyrase I enzyme as a target showed how the studied heterocyclic compounds act as a ligand interacting most of active sites on Tankyrase I with a type of interactions specified for H-bonding and VDW. We investigated that the five studied ligands act as inhibitors for different active sites along the target. The molecular docking study also revealed that the compound 6c was the most effective compounds in inhibiting Tankyrase I enzyme (2rf5), this result can help strongly in inhibition of carcinogenic cells and cancer treatment.

A perception into binary and ternary copper (II) complexes: synthesis, characterization, DFT modeling, antimicrobial activity, protein binding screen, and amino acid interaction

“…1 b-i), but no change in the maximum emission wavelength of HPf was observed. This observation could be attributed to the high affinity of Cu 2+ ions to the carbonyl and carboxylic groups present in the pefloxacin molecule as a ligand [ 53 ] and that the ion can strongly quench the inner fluorescence of the pefloxacin ligand and that the interaction between the bioligand and metal ion indeed existed without inducing any conformational change in pefloxacin. Static quenching implies either the existence of a sphere of effective quenching or the formation of a ground state nonfluorescent complex.…”

Huangqi Guizhi Wuwu decoction in peripheral neurotoxicity treatment using network pharmacology and molecular docking

“…Gas chromatography and spectroscopy are commonly used to determine the crystal structure of separated chemical components. [22,23] In order to fully apply the database to save research costs and reflect the role of computer technology in drug research and development, the molecular structure of 6-Gingerol (PubChem CID: 442793) and nuciferin (PubChem CID: 10146) was selected from the public chemistry database (PubChem), converted into a three-dimensional structure with ChemBio3D Ultra12.0, [24] and optimized using the MMFF94 force field (Hagler, 1996). To evaluate the interaction mode of 6-Gingerol and Nuciferin with SLC6A2 (Sodium-dependent noradrenaline transporter), SLC6A3 (Sodium-dependent dopamine transporter), and SLC6A4 (Sodium-dependent serotonin transporter) proteins, AutoDock Vina 1.1.2 [25] was used.…”

Synthesis and Screening of New [1,3,4]Oxadiazole, [1,2,4]Triazole, and [1,2,4]Triazolo[4,3-b][1,2,4]triazole Derivatives as Potential Antitumor Agents on the Colon Carcinoma Cell Line (HCT-116)

“…As we mentioned in our recent articles, triazolo compounds and particular [1,2,4]­triazolo derivatives are well known to have many physiological activities, such as anticancer. , Also, [1,2,4]­triazole derivatives have been reported as antimicrobial, insecticidal, fungicidal, antidepressant, hypnotic, anti-inflammatory, antihypertensive, and plant growth regulator. − On the other hand, 1,3,4-oxadiazole has become an essential building unit for the creation of new drugs where a literature survey showed that a slight systemic change in 1,3,4-oxadiazole moiety structure could lead to qualitative as well as quantitative changes in 1,3,4-oxadiazole derivative activity, which convinced us to start synthesizing different new 1,3,4-oxadiazole derivatives in order to increase their activity and lower their toxicity. Over the last 2 decades, the synthesis of novel 1,3,4-oxadiazole derivatives and the investigation into their chemical properties and biological behavior have increased. − Also, the combination of oxadiazole and other heterocycles such as pyrrole and pyrazole rings in one compound led to several biological activities of these compounds. − We may therefore conclude that 1,3,4-oxadiazole is one of the main pharmacophores that plays an important role in pharmaceutical chemistry and has a broad range of important biological activities including anti-inflammatory, , anticancer, − antimalarial, antibacterial, − anticonvulsant, antitubercular, − anti-allergic agent, analgesic, and vasodilator .…”